Structural highlights
Function
[DACH1_HUMAN] Transcription factor that is involved in regulation of organogenesis. Seems to be a regulator of SIX1, SIX6 and probably SIX5. Corepression of precursor cell proliferation in myoblasts by SIX1 is switched to coactivation through recruitment of EYA3 to the SIX1-DACH1 complex. Transcriptional activation seems also to involve association of CREBBP. Seems to act as a corepressor of SIX6 in regulating proliferation by directly repressing cyclin-dependent kinase inhibitors, including the p27Kip1 promoter (By similarity). Inhibits TGF-beta signaling through interaction with SMAD4 and NCOR1. Binds to chromatin DNA via its DACHbox-N domain (By similarity).[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The Dachshund proteins are essential components of a regulatory network controlling cell fate determination. They have been implicated in eye, limb, brain, and muscle development. These proteins cannot be assigned to any recognizable structural or functional class based on amino acid sequence analysis. The 1.65 A crystal structure of the most conserved domain of human DACHSHUND is reported here. The protein forms an alpha/beta structure containing a DNA binding motif similar to that found in the winged helix/forkhead subgroup of the helix-turn-helix family. This unexpected finding alters the previously proposed molecular models for the role of Dachshund in the eye determination pathway. Furthermore, it provides a rational framework for future mechanistic analyses of the Dachshund proteins in several developmental contexts.
Structure of the retinal determination protein Dachshund reveals a DNA binding motif.,Kim SS, Zhang RG, Braunstein SE, Joachimiak A, Cvekl A, Hegde RS Structure. 2002 Jun;10(6):787-95. PMID:12057194[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wu K, Yang Y, Wang C, Davoli MA, D'Amico M, Li A, Cveklova K, Kozmik Z, Lisanti MP, Russell RG, Cvekl A, Pestell RG. DACH1 inhibits transforming growth factor-beta signaling through binding Smad4. J Biol Chem. 2003 Dec 19;278(51):51673-84. Epub 2003 Oct 2. PMID:14525983 doi:http://dx.doi.org/10.1074/jbc.M310021200
- ↑ Kim SS, Zhang RG, Braunstein SE, Joachimiak A, Cvekl A, Hegde RS. Structure of the retinal determination protein Dachshund reveals a DNA binding motif. Structure. 2002 Jun;10(6):787-95. PMID:12057194
